tbuckley/cabot-search huggingface dataset:
Genomic and Transcriptomic Characteristics of Metastatic Thyroid Cancers with Exceptional Responses to Radioactive Iodine Therapy
Authors: Laura Boucai, Mahesh Saqcena, Fengshen Kuo, Ravinder K. Grewal, Nicholas Socci, Jeffrey A. Knauf, Gnana P. Krishnamoorthy, Mabel Ryder, Alan L. Ho, Ronald A. Ghossein, Luc G.T. Morris, Venkatraman Seshan, James A. Fagin
Journal: Clinical Cancer Research (2023)

The determinants of response or resistance to radioiodine (RAI) are unknown. We aimed to identify genomic and transcriptomic factors associated with structural responses to RAI treatment of metastatic thyroid cancer, which occur infrequently, and to test whether high MAPK pathway output was associated with RAI refractoriness.Exceptional response to RAI was defined as reduction of tumor volume based on RECIST v1.1. We performed a retrospective case-control study of genomic and transcriptomic characteristics of exceptional responders (ER; n = 8) versus nonresponders (NR; n = 16) matched by histologic type and stage at presentation on a 1:2 ratio.ER are enriched for mutations that activate MAPK through RAF dimerization (RAS, class 2 BRAF, RTK fusions), whereas NR are associated with BRAFV600E, which signals as a monomer and is unresponsive to negative feedback. ER have a lower MAPK transcriptional output and a higher thyroid differentiation score (TDS) than NR (P < 0.05). NR are enriched for 1q-gain (P < 0.05) and mutations of genes regulating mRNA splicing and the PI3K pathway. BRAFV600E tumors with 1q-gain have a lower TDS than BRAFV600E/1q-quiet tumors and transcriptomic signatures associated with metastatic propensity.ER tumors have a lower MAPK output and higher TDS than NR, whereas NR have a high frequency of BRAFV600E and 1q-gain. Molecular profiling of thyroid cancers and further functional validation of the key findings discriminating ER from NR may help predict response to RAI therapy.
Apolipoprotein C3 induces inflammasome activation only in its delipidated form
Authors: Cheng-Chieh Hsu, Baohai Shao, Jenny E. Kanter, Yi He, Tomas Vaisar, Joseph L. Witztum, Janet Snell-Bergeon, Gregory McInnes, Shannon Bruse, Omri Gottesman, Adam E. Mullick, Karin E. Bornfeldt
Journal: Nature Immunology (2023)
Cell-Free Urine and Plasma DNA Mutational Analysis Predicts Neoadjuvant Chemotherapy Response and Outcome in Patients with Muscle-Invasive Bladder Cancer
Authors: Emil Christensen, Iver Nordentoft, Karin Birkenkamp-Demtröder, Sara K. Elbæk, Sia V. Lindskrog, Ann Taber, Tine G. Andreasen, Trine Strandgaard, Michael Knudsen, Philippe Lamy, Mads Agerbæk, Jørgen B. Jensen, Lars Dyrskjøt
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To investigate the use of plasma and urine DNA mutation analysis for predicting neoadjuvant chemotherapy (NAC) response and oncological outcome in patients with muscle-invasive bladder cancer. Experimental Design: Whole-exome sequencing of tumor and germline DNA was performed for 92 patients treated with NAC followed by radical cystectomy (RC). A custom NGS-panel capturing approximately 50 mutations per patient was designed and used to track mutated tumor DNA in plasma and urine. A total of 447 plasma samples, 281 urine supernatants, and 123 urine pellets collected before, during, and after treatment were analyzed. Patients were enrolled from 2013 to 2019, with a median follow-up time of 41.3 months after RC. Results: We identified tumor DNA before NAC in 89% of urine supernatants, 85% of urine pellets, and 43% of plasma samples. Tumor DNA levels were higher in urine supernatants and urine pellets compared with plasma samples (P &amp;lt; 0.001). In plasma, detection of circulating tumor DNA (ctDNA) before NAC was associated with a lower NAC response rate (P &amp;lt; 0.001). Detection of tumor DNA after NAC was associated with lower response rates in plasma, urine supernatant, and urine pellet (P &amp;lt; 0.001, P = 0.03, P = 0.002). Tumor DNA dynamics during NAC was predictive of NAC response and outcome in urine supernatant and plasma (P = 0.006 and P = 0.002). A combined measure from plasma and urine supernatant tumor DNA dynamics stratified patients by outcome (P = 0.003). Conclusions: Analysis of tumor DNA in plasma and urine samples both separately and combined has a potential to predict treatment response and outcome.
Errors in Figures
Authors: Miles Weinberger, Zhengxiu Luo
Journal: JAMA Pediatrics (2023)

Maria T. Maza, BS; Kara A. Fox, MA; Seh-Joo Kwon, BS; Jessica E. Flannery, PhD; Kristen A. Lindquist, PhD; Mitchell J. Prinstein, PhD; Eva H. Telzer, PhD
Analysis of Silver Alert Reporting System Activations for Missing Adults With Dementia in Texas, 2017 to 2022
Authors: Anthony D. McDonald, Valerie Danesh, John M. Ray, Alan B. Stevens
Journal: JAMA Network Open (2023)

This cross-sectional study analyzes data from Silver Alert activations in Texas from 2017 to 2022 to identify temporal, geographic, and wandering characteristics of missing adults with dementia.
Outcomes Among Undocumented Immigrant Kidney Transplant Recipients in California
Authors: Natsuki Eguchi, Ekamol Tantisattamo, Dean Chung, Uttam G. Reddy, Antoney Ferrey, Donald Dafoe, Hirohito Ichii
Journal: JAMA Network Open (2023)

There are over 2 million undocumented immigrants (UI) in California, where currently, all individuals regardless of immigration status have access to kidney transplant. There is a medical perception that UI face a higher risk of transplant failure due to language barriers and lack of access to immunosuppressive medication and health care when compared with US residents (UR).To elucidate the kidney transplant outcomes of UI at an academic medical center in California.A retrospective cohort study was conducted from a single transplant center during an 8-year study period. Patients who received a kidney transplant at the University of California, Irvine, between January 1, 2012, and September 1, 2019, were included in this study. Data were analyzed from October 2020 to August 2021.The primary exposure of this study was citizenship status. UI were defined as immigrants residing in the US without permission or legal documentation.The primary end point was all-cause graft loss defined as the return to dialysis, need for a second kidney transplant, or death. The secondary end points of this study were all-cause mortality and rejection. All-cause mortality between the 2 groups was compared using multiple Cox proportional hazard regression analysis. Other transplant outcomes, including all-cause graft loss and acute rejection, were examined by competing risks regressions with mortality and mortality plus graft loss serving as competing risks, respectively.Of all 446 consecutive kidney transplant recipients, the mean (SD) age was 47 (13) years; 261 patients (59%) were male, and 114 (26%) were UI. During a median (IQR) follow-up time of 3.39 (0.04-8.11) years, 6 UI and 48 UR experienced all-cause graft loss. UR had a 192% (hazard ratio, 2.92; 95% CI, 1.21-6.85; P = .01) and 343% (hazard ratio, 4.34; 95% CI, 1.05-18.69; P = .04) significantly increased unadjusted risk for all-cause graft loss and all-cause mortality, respectively. These results became nonsignificant and were mostly attenuated when adjusted for age and ethnicity. Finally, there was no difference in incidence rate of kidney allograft rejection between the 2 groups (UR, 3.5 per 100 person-years vs UI, 2.4 per 100 person-years; rate ratio, 1.45; 95% CI, 0.90-5.05; P = .08).This single-center cohort study found that kidney transplant outcomes of UI were not inferior to those of UR. Across the US, however, UI have consistently had unequal access to transplantation. These findings suggest that extending kidney transplants to UI is safe and does not portend worse outcomes. As a result, denying transplant according to immigration status not only results in higher costs but also worse end stage kidney disease outcomes for an already underserved population.
Time-Limited Trials of Intensive Care Unit Care
Authors: John J. Popovich, Isadore Budnick, Thanh H. Neville
Journal: JAMA Internal Medicine (2023)

This Teachable Moment discusses time-limited trials, “an agreement between clinicians and a patient/family to use certain medical therapies over a defined period to see if the patient improves or deteriorates according to agreed-on clinical outcomes.”.
Uncommon Culprit Vessel of de Winter Electrocardiogram Pattern
Authors: Chia-Chen Chen, Bin-Yu Cai, Xue-Wei Qi
Journal: JAMA Internal Medicine (2023)

This case report describes a patient in their 50s who presented to the emergency department with perspiration, persistent and squeezing chest pain, and chest distress that had persisted for 90 minutes without relief.
Melanoma Incidence by Sex, Indoor Tanning, and Body Site
Authors: Mengyang He, Jinchang Huang
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
A Systematic Review and Multilevel Regression Analysis Reveals the Comorbidity Prevalence in Cancer
Authors: Cilla E.J. Vrinzen, Linn Delfgou, Niek Stadhouders, Rosella P.M.G. Hermens, Matthias A.W. Merkx, Haiko J. Bloemendal, Patrick P.T. Jeurissen
Journal: Cancer Research (2023)

Comorbidities can have major implications for cancer care, as they might impact the timing of cancer diagnosis, compromise optimal care, affect treatment outcomes, and increase healthcare costs. Thus, it is important to comprehensively evaluate cancer comorbidities and examine trends over time. Here, we performed a systematic literature review on the prevalence and types of comorbidities for the five most common forms of cancer. Observational studies from Organisation for Economic Co-operation and Development countries published between 1990 and 2020 in English or Dutch that used routinely collected data from a representative population were included. The search yielded 3,070 articles, of which, 161 were eligible for data analyses. Multilevel analyses were performed to evaluate determinants of variation in comorbidity prevalence and trends over time. The weighted average comorbidity prevalence was 33.4%, and comorbidities were the most common in lung cancer (46.7%) and colorectal cancer (40.0%), followed by prostate cancer (28.5%), melanoma cancer (28.3%), and breast cancer (22.4%). The most common types of comorbidities were hypertension (29.7%), pulmonary diseases (15.9%), and diabetes (13.5%). After adjusting for gender, type of comorbidity index, age, data source (patient records vs. claims), and country, a significant increase in comorbidities of 0.54% per year was observed. Overall, a large and increasing proportion of the oncologic population is dealing with comorbidities, which could be used to inform and adapt treatment options to improve health outcomes and reduce healthcare costs.Comorbidities are frequent and increasing in patients with cancer, emphasizing the importance of exploring optimal ways for uniform comorbidity registration and incorporating comorbidity management into cancer care.
Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma
Authors: Lijun Yao, Julia T. Wang, Reyka G. Jayasinghe, Julie O'Neal, Chia-Feng Tsai, Michael P. Rettig, Yizhe Song, Ruiyang Liu, Yanyan Zhao, Omar M. Ibrahim, Mark A. Fiala, Julie M. Fortier, Siqi Chen, Leah Gehrs, Fernanda Martins Rodrigues, Michael C. Wendl, Daniel Kohnen, Andrew Shinkle, Song Cao, Steven M. Foltz, Daniel Cui Zhou, Erik Storrs, Matthew A. Wyczalkowski, Smrithi Mani, Scott R. Goldsmith, Ying Zhu, Mark Hamilton, Tao Liu, Feng Chen, Ravi Vij, Li Ding, John F. DiPersio
Journal: Cancer Research (2023)

Abstract Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA sequencing reiterated top candidates, further affirming the ability of single-cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy. Significance: Single-cell transcriptomic profiling and multiomic cross-validation to uncover therapeutic targets identifies 38 myeloma marker genes, including 11 transcribing surface proteins with previously uncharacterized potential for targeted antitumor therapy.
Effect of Vitamin D Supplementation on Bone Mass in Infants With 25-Hydroxyvitamin D Concentrations Less Than 50 nmol/L
Authors: Nathalie Gharibeh, Maryam Razaghi, Catherine A. Vanstone, Olusola F. Sotunde, Laura Glenn, Kristina Mullahoo, Zahra Farahnak, Ali Khamessan, Shu Qin Wei, Dayre McNally, Frank Rauch, Glenville Jones, Martin Kaufmann, Hope A. Weiler
Journal: JAMA Pediatrics (2023)

The dose of supplemental vitamin D needed in infants born with serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L (ie, 20 ng/mL) is unclear.To determine whether a higher dose (1000 IU vs 400 IU per day) is required in infants born with 25(OH)D concentrations less than 50 nmol/L for bone mineral accretion across infancy.In this prespecified secondary analysis of a double-blinded randomized clinical trial, conducted from March 2016 to March 2019 in a single center in Greater Montreal, Quebec, Canada, a consecutive sample of 139 healthy term singletons were recruited from 866 infants screened for vitamin D status at birth. Data were analyzed from June 2021 to November 2022.Capillary blood was collected 24 to 36 hours after birth to measure serum total 25(OH)D concentrations. Infants with 25(OH)D concentrations less than 50 nmol/L were randomized to receive either 1000 IU or 400 IU per day of oral vitamin D3 supplementation from age 1 to 12 months. Infants with 25(OH)D concentrations of 50 nmol/L or greater formed a reference group.Measures at age 1, 3, 6, and 12 months were preplanned and included whole-body bone mineral content, lumbar spine bone mineral content, and bone mineral density using dual-energy x-ray absorptiometry, and serum 25(OH)D3 using liquid chromatography tandem mass spectrometry.Of 139 included infants, 81 (58.3%) were male, and the median (IQR) gestational age at birth was 39.6 (38.9-40.6) weeks. A total of 49 infants were included in the 1000 IU per day group, 49 infants in the 400 IU per day group, and 41 in the reference group. Mean (SD) whole-body bone mineral content was not different between trial groups over time (1000 IU per day, 173.09 [2.36] g; 400 IU per day, 165.94 [66.08] g). Similarly, no differences were observed in lumbar spine bone mineral content or density. Mean (SD) serum 25(OH)D3 concentrations were significantly higher in the 1000 IU per day group from age 3 to 12 months (3 months, 115.2 [35.3] nmol/L; 6 months, 121.6 [34.4] nmol/L; 12 months, 99.6 [28.8] nmol/L) compared with the 400 IU per day trial group (3 months, 77.4 [23.3] nmol/L; 6 months, 85.1 [18.6] nmol/L; 12 months, 82.3 [14.3] nmol/L).In this study, a higher dose of vitamin D supplementation in infants born with 25(OH)D concentrations less than 50 nmol/L did not present advantages to bone mass in infancy. This study supports a standard dose of 400 IU per day of vitamin D supplementation for breastfed infants in Montreal.ClinicalTrials.gov Identifier: NCT02563015.
Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Evolves from<i>TP53</i>-Mutated Clonal Hematopoiesis
Authors: Ryunosuke Saiki, Seishi Ogawa
Journal: Blood Cancer Discovery (2023)

Low-hypodiploid acute lymphoblastic leukemia (LH-ALL) in both children and adults is characterized by biallelic TP53 alterations in virtually all cases. However, in contrast to a common germline origin of the TP53 mutations in pediatric cases, those in adult cases are mostly somatic and are derived from age-related clonal hematopoiesis (ARCH), highlighting the role of TP53-mutant ARCH in the development not only of myeloid leukemogenesis but also of LH-ALL in aged populations. See related article by Kim et al., p. 134 (4).
Changes in the Rate of Leucine-Rich Glioma-Inactivated 1 Seropositivity During the COVID-19 Lockdown
Authors: Adam E. Handel, Jacqueline Palace, Elizabeth Bateman, Patrick Waters, Sarosh R. Irani
Journal: JAMA Neurology (2023)

This case-control study investigates the positivity rates of the most prevalent neuroglial surface antibodies during the COVID-19 pandemic.
Errors in Methods Section and Supplement
Journal: JAMA Network Open (2023)

Austin D. Vo, BS; Jennifer La, PhD; Julie T.-Y. Wu, MD; Judith M. Strymish, MD; Matthew Ronan, MD; Mary Brophy, MD; Nhan V. Do, MD; Westyn Branch-Elliman, MD, MMSc; Nathanael R. Fillmore, PhD; Paul A. Monach, MD, PhD
Race and the 2022 American Academy of Pediatrics Hyperbilirubinemia Guideline
Authors: William Christopher Golden
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Changes in Body Mass Index Among School-Aged Youths Following Implementation of the Healthy, Hunger-Free Kids Act of 2010
Authors: Aruna Chandran, Mohamad Burjak, Joshua Petimar, Ghassan Hamra, Melissa M. Melough, Anne L. Dunlop, Brittney M. Snyder, Augusto A. Litonjua, Tina Hartert, James Gern, Akram N. Alshawabkeh, Judy Aschner, Carlos A. Camargo, Dana Dabelea, Cristiane S. Duarte, Assiamira Ferrara, Jody M. Ganiban, Frank Gilliland, Diane R. Gold, Monique Hedderson, Julie B. Herbstman, Christine Hockett, Margaret R. Karagas, Jean M. Kerver, Kathleen A. Lee-Sarwar, Barry Lester, Cindy T. McEvoy, Zhongzheng Niu, Joseph B. Stanford, Rosalind Wright, Emily Zimmerman, Shohreh Farzan, Zhumin Zhang, Emily Knapp
Journal: JAMA Pediatrics (2023)

Importance The prevalence of obesity among youths 2 to 19 years of age in the US from 2017 to 2018 was 19.3%; previous studies suggested that school lunch consumption was associated with increased obesity. The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) strengthened nutritional standards of school-based meals. Objective To evaluate the association between the HHFKA and youth body mass index (BMI). Design, Setting, and Participants This cohort study was conducted using data from the Environmental Influences on Child Health Outcomes program, a nationwide consortium of child cohort studies, between January 2005 and March 2020. Cohorts in the US of youths aged 5 to 18 years with reported height and weight measurements were included. Exposures Full implementation of the HHFKA. Main Outcomes and Measures The main outcome was annual BMI z -score (BMIz) trends before (January 2005 to August 2016) and after (September 2016 to March 2020) implementation of the HHFKA, adjusted for self-reported race, ethnicity, maternal education, and cohort group. An interrupted time-series analysis design was used to fit generalized estimating equation regression models. Results A total of 14 121 school-aged youths (7237 [51.3%] male; mean [SD] age at first measurement, 8.8 [3.6] years) contributing 26 205 BMI measurements were included in the study. Overall, a significant decrease was observed in the annual BMIz in the period following implementation of the HHFKA compared with prior to implementation (−0.041; 95% CI, −0.066 to −0.016). In interaction models to evaluate subgroup associations, similar trends were observed among youths 12 to 18 years of age (−0.045; 95% CI, −0.071 to −0.018) and among youths living in households with a lower annual income (−0.038; 95% CI, −0.063 to −0.013). Conclusions and Relevance In this cohort study, HHFKA implementation was associated with a significant decrease in BMIz among school-aged youths in the US. The findings suggest that school meal programs represent a key opportunity for interventions to combat the childhood obesity epidemic given the high rates of program participation and the proportion of total calories consumed through school-based meals.
Errors in Figure 2
Journal: JAMA Network Open (2023)

Randy A. Vince Jr, MD, MS; Ralph Jiang, BS; Merrick Bank, BS; Jake Quarles, BS; Milan Patel, MD; Yilun Sun, PhD; Holly Hartman, PhD; Nicholas G. Zaorsky, MD, MS; Angela Jia, MD; Jonathan Shoag, MD; Robert T. Dess, MD; Brandon A. Mahal, MD; Kristian Stensland, MD, MPH; Nicholas W. Eyrich, MD, MS; Mariana Seymore, BS; Rebecca Takele, BS; Todd M. Morgan, MD; Matthew Schipper, PhD; Daniel E. Spratt, MD